PROJECT SUMMARY/ABSTRACT Despite great strides in improving the volume coverage, temporal resolution, and dose efficiency of clinical CT scanners, the spatial resolution has plateaued since the mid-1980s. Nevertheless, there is a clear clinical need to reveal a new level of anatomic detail for CT imaging in multiple areas, including assessment of bone fractures, bone microarchitecture and fracture risk, spinal stenosis, spinal fusion healing after surgery, and cochlear im- plant placement. Various attempts have been made to improve the spatial resolution of CT, but the improvements have been incremental and there is still no practical solution that can enable in vivo ultra-resolution imaging on standard clinical CT scanners: a redesign of the CT detector array to one with finer pitched cells is very expensive for widespread application, while high-resolution extremity CT and flat-panel CT have limited bore size and suffer from inherent image quality issues, respectively. We propose a new ultra-resolution CT technique, named ?Zoomed-In Partial Scan? (ZIPS), to achieve a ma- jor improvement in the spatial resolution of standard, clinical CT. The increased spatial resolution is achieved by combining an extra small focal spot with a large magnification, and with innovative scanning schemes and re- construction algorithms. The ZIPS method can be incorporated on existing standard clinical CT scanners, with- out a costly redesign of the CT detector based on smaller cells or sacrificing image quality or dose efficiency in regular scans. Compared with various specialized high-resolution research CT scanners, the proposed ZIPS method leverages the accessibility, versatility, and wide volume coverage of standard clinical CT to provide an in vivo ultra-resolution option for a wide patient population and various anatomical regions. The project combines CT systems and reconstruction expertise at GE Research Center and clinical applica- tion expertise at the Hospital for Special Surgery (HSS) and the Massachusetts Eye and Ear Institute (MEEI). The GE Research Center team will perform all technical developments of this project. The HSS team will lead an ex vivo validation study of the ZIPS CT technique applied to bone microstructure analysis, and compare results with CT gold standard and standard clinical CT. MEEI will provide clinical expertise in the evaluation of ZIPS CT for temporal bone imaging.